This collaborative proposal involves the structural determination of the binding sites of neurotrophins to their receptors using chemical cross-linking, isolation of the ligand receptor complexes, their proteolytic digestion and structural analysis by advanced methods of mass spectrometry. In addition, mass spectrometric methods will be developed to establish the purity of synthetic neurotrophins as well as to monitor the secretion, uptake and retrograde transport of specific neurotrophins in neurons. Carbon-14 labelled neurotrophins will be used to identify receptor sub-types using 2-d gels and accelerator mass spectrometry followed by receptor identification using tandem mass spectrometry for amino acid sequencing of labelled bands.